Sideritis in mood disorders and ADHD

Extracts of Sideritis scardica as inhibitors of monoamine transporters:
A pharmacological mechanism for efficacy in mood disorders and attention-deficit
hyperactivity disorder (ADHD)
Rainer Knörle
Aim of the study: Sideritis species are traditionally used within the mediterranean area for the cure of cold cough
and for the treatment of gastrointestinal disorders. The aim of this study was to investigate the effects of Sideritis
scardica extracts on the monoamine transporters and to derive possible medicinal applications from the
pharmacological profile of the extracts.
Methods: We have studied the effect of various Sideritis scardica extracts on serotonin, noradrenaline and
dopamine uptake into rat brain synaptosomes and serotonin uptake into human JAR cells.
Results: All extracts inhibited the uptake of all three monoamines into rat brain synaptosomes by their respective
transporters, the alcoholic extracts being more effective than the water extract. EC50 values were in the range of
30-40 µg/ml. Inhibition of the human serotonin transporter by the methanol extract was even more effective
(EC50: 1,4 µg/ml). Combining Sideritis ethanol extract and fluvoxamine resulted in a leftward shift of the
fluvoxamine concentration-response curve.
Conclusions: The pharmacological profile of Sideritis scardica extracts suggests their use in the phytochemical
therapy of mental disorders associated with a malfunctioning monoaminergic neurotransmission, like major
depression or the attention-deficit hyperactivity disorder.
1. Introduction
The genus Sideritis (Lamiaceae) comprises about
150 species distributed mainly in the mediterranean
area and in the moderate zones of Asia. The taxa
are attributed to three sections: sect. Sideritis, sect.
Empedoclia (Rafin.) Bentham. and sect. Hesiodora
Bentham. They are growing in low-fertility hilly
and mountainous areas at over 800-1000 m altitude
(1,2).
Plants of the genus Sideritis are widely used in folk
medicine in the eastern mediterranean area for the
cure of cold cough and for the treatment of
gastrointestinal disorders. This is due to their antiinflammatory
(3,4), antibacterial and antifungal
(5,6) activities. Studies on the pharmacological
action of Sideritis revealed diuretic (7), antioxidant
(8) and analgesic effects (9).
Sideritis has become very fashionable in Germany
recently and is found in a variety of shops marketed
as “Bergtee” or “Griechischer Bergtee”. The herb is
sold cut or sometimes even whole, the latter making
identification much easier. The majority of species
sold in Germany consists of Sideritis syriaca,
Sideritis dichotoma and Sideritis scardica. The
important role of the leaves and flowering tops of
Sideritis as traditional tea in the eastern
mediterranean area and Spain (mountain tea,
malotira, dag cay, té de puerto) has imposed the
need of cultivation of Sideritis since the production
from wild-collected plants was insufficient to cover
the demand of market.
The chemical constituents of Sideritis have been
investigated for a long time. The essential oil of all
Sideritis species mainly consists of α-pinene, βpinene,
β-caryophyllene, caryophyllene oxide,
limonene, 1,8-cineole, carvacrol, myrcene,
germacrene D, spathulenol, α-bisabolol, fenchone
and sabinene (10,11). The main components vary
between the species. In addition, 8-hydroxyflavone
allosylglucosides and p-coumaroylglucosides are
found in several Sideritis species (12). For some
species the presence of phenylpropanoid glycosides
(3) or kaurane diterpenoids (13,14) is reported.
Andalusol (ent-6α-8α-18-trihydroxy-13(16),14labdadiene),
a diterpene found in Sideritis foetens,
has been shown to inhibit iNOS expression in
macrophages. It is supposed that this effect is
caused by a transcriptional mechanism. This
inhibition of iNOS by andalusol and related
substances might be responsible for the antiinflammatory
effect of Sideritis species, since iNOS
is the enzyme responsible for the high-output NO
synthesis (15).
An imbalance in monoaminergic neurotransmission
is considered to be responsible for a multitude of
mood disorders. Mood disorders and conditions of
impaired or diminished cognition and attention
affect more than one in every four persons in the
developed world. Representative examples include
depressive disorders, generalised anxiety disorders
or the attention-deficit hyperactivity disorder. In the
central nervous system, dopamine is involved in
controlling locomotion, cognition, affect and mood,
noradrenaline is involved in modulating attention,

working memory, behavioural inhibition, planning,
alertness, arousal, mood and vigilance. Serotonin
plays a role in mood, aggression, anxiety, appetite,
sleep, cognition, learning and locomotion.
Most antidepressants increase synaptic levels of the
monoamine neurotransmitter serotonin. They may
also enhance the levels of two other
neurotransmitters, noradrenaline and dopamine.
This observation gave rise to the monoamine
hypothesis of depression. In its contemporary
formulation, the monoamine hypothesis postulates
that the deficit of certain neurotransmitters is
responsible for the corresponding features of
depression. There are several different monoamine
transporters: the dopamine transporter DAT, the
noradrenaline transporter NET and the serotonin
transporter SERT. Modern antidepressants typically
work by binding to the corresponding transporter
and thereby inhibiting serotonin, noradrenaline or
dopamine reuptake and raising active levels in the
synapse (16).
Attention-deficit hyperactivity disorder (ADHD) is
a heterogeneous behavioural disorder characterised
by inattention or lack of focus, hyperactivity and
impulsivity. Recent genetic and neuroimaging
studies provide evidence for contributions of a
monoaminergic dysfunction in ADHD. The
efficacy of medications that stimulate the
dopaminergic and noradrenergic systems suggests
that normalizing their activities in relevant brain
areas is necessary for the treatment of ADHD (17).
Especially in the case of central nervous system
disorders, a large majority of the patients would
prefer nature medicine (18). Example of plants with
central nervous action are Valeriana officinalis
(valerian) and Humulus lupulus (hops), both used
for sleep disturbances, or Passiflora incarnata
(passion fruit) and Hypericum perforatum (St.
John’s wort) used for the treatment of affective
disorders.
Although Hypericum extracts are well established
in the phytotherapy of depression, it would be
desirable to have other phytopharmaceutical entities
with a proof of action for the therapy of central
nervous disorders caused by an imbalance in
monoamine neurotransmission. The aim of this
study was to investigate the effects of Sideritis
scardica extracts on the monoamine transporters
and to derive possible medicinal applications from
the pharmacological profile of the extracts.
2. Materials and methods
2.1 Plant extracts
Farm-cultivated aerial parts of Sideritis scardica
were obtained from Tee Gschwendner,
Meckenheim, Germany (Product No.: 1127, Lot:
PSA07080901). The raw plant material was
analysed and characterised at the trader’s
laboratory. Voucher specimens of the crude
botanicals are deposited at the trader’s facilities.
The dry herb was ground and extracts were
prepared by boiling the plant material for 1 h under
reflux with the respective solvent (water, methanol,
70% ethanol). The extracts were filtered and dried
by rotary evaporation. Yields of the extract was
320-340 mg (water extract), 100-120 mg per g plant
material (methanol extract) and 200-240 mg extract
per g plant material (70% ethanol extract).
2.2 Monoamine uptake experiments
2.2.1 Rat brain synaptosome experiments
Male Wistar rats (250-300 g) were decapitated
under CO2 anaesthesia and the brain was quickly
removed. Cortex was prepared on ice. The cortical
tissue was homogenised in 10 volumes ice cold
0.32 M sucrose/10 mM HEPES pH 7,4. The
homogenate was centrifuged for 10 min at 4° C and
900*g. The supernatant was centrifuged again for
10 min at 4° C and 11000*g. The supernatant was
discarded and the pellet was kept on ice. At the
beginning of the experiment, the pellet was
resuspended in buffer to yield a suspension with a
total protein content of 20-30 µg/ml.
The uptake experiments were performed in 96 well
filter plates (GF-C glass fiber filter Multiscreen FB,
Millipore, Schwalbach, Germany). Each well was
washed with 250 µl of buffer containing 121 mM
NaCl, 1.8 mM KCl, 1.3 mM CaCl2, 1.2 mM
MgSO4, 25 mM NaHCO3, 1.2 mM KH2PO4, 11
mM glucose, 0.57 mM ascorbic acid, saturated with
95% O2/5% CO2, final pH 7.4. 50 µM pargyline
were added for the inhibition of MAO. 50 µl
synaptosome preparation in buffer was added to
each well and incubated with various
concentrations of extracts dissolved in DMSO (final
concentration of DMSO 10 µl/well, 8 wells per
extract concentration) in a total volume of 240 µl
for 10 min. After addition of 10 µl of a 100 nM
serotonin solution in buffer containing 0.1 µCi of
[³H]-serotonin the plates were incubated for 10 min
at room temperature, the uptake buffer was then
rapidly filtered off, and the filter was washed three
times with 250 µl buffer. The filters were punched
out and transferred into scintillation vials for liquid
scintillation counting. Nonspecific uptake was
defined as uptake in the presence of 10 µM
fluvoxamine.
Noradrenaline and dopamine uptake experiments
were performed as described above. The final
concentrations of radiolabelled transmitter were 20
nM ([³H]-noradrenaline) or 10 nM ([³H]dopamine).
The plates were incubated for 15 min at
37° C. Unspecific binding was determined in the
presence of 10 µM nomifensine.
2

2.2.2 Uptake experiments using JAR cells
In addition, serotonin uptake experiments were
performed with human placental choriocarcinoma
cells (JAR) which constitutively express the human
serotonin transporter hSERT.
JAR cells (DSMZ, Braunschweig, Germany) were
grown in RPMI-1640 medium containing Lglutamine,
10% foetal calf serum, 100 U/ml
penicillin, and 100 mg/ml streptomycin at 37° C in
an atmosphere of 5% CO2, 95% air. The uptake
experiments were performed in poly-(D-lysine)coated
24-well plates (1 day after plating; 50000 -
200000 cells/well). Each well was washed twice
with 1 ml of buffer containing 10 mM HEPES, 120
mM NaCl, 3 mM KCl, 2 mM CaCl2, 2 mM MgCl2,
5 mM glucose and 0.57 mM ascorbic acid final pH
7.3 and incubated with various concentrations of
extracts dissolved in DMSO (final concentration of
DMSO 10 µl/well, 4 wells per concentration) in a
total volume of 1 ml. After addition of 10 µl of a
100 nM serotonin solution in buffer containing 0.1
µCi of [³H]-serotonin the plates were incubated for
10 min at room temperature, the uptake buffer was
then rapidly aspirated, and the cells were washed
three times with 1 ml buffer. Cells were lysed with
0.5 ml of 0.5 M NaOH and transferred into
scintillation vials for liquid scintillation counting.
Nonspecific uptake was defined as uptake in the
presence of 10 µM fluvoxamine.
2.3 Effect of Sideritis scardica extracts on
cell viability
The effect of Sideritis scardica extracts on cell
viability was investigated by measuring lactate
dehydrogenase (LDH), an enzyme located
intracellularily which is released into the
extracellular space when the cells are damaged.
Sideritis extracts were investigated in
concentrations of 50 µg/ml and 500 µg/ml. The
JAR cells were incubated at 20° C with the extracts
in uptake buffer for 3 h. Assay conditions were
adopted from Bergmeyer and Bernt (19). Briefly,
100 µl 69 mM sodium pyruvate in 100 mM sodium
phosphate buffer pH 7.5 were added to 2.8 ml 0,13
mM β-NADH solution in sodium phosphate buffer.
100 µl of JAR cell supernatant (or 100 µl buffer for
the control experiments) was added and the change
in absorption at 340 nm was recorded at fixed times
of 15 min, 30 min and 45 min.
2.4 Statistics
Radioactivity accumulated in the filters was
normalised as “percent of specific uptake” always
referring to the specific uptake obtained from total
minus non-specific uptake. EC50 values were
calculated from the normalised data using iterative
curve fitting routines (SigmaPlot® 8.0, SPSS
Science, Chicago, Illinois, USA). The errors given
in this paper represent standard error of mean
(S.E.M.).
3. Results
3.1 Rat brain synaptosomes
Concentration-response curves were recorded for
the inhibition of the monoamine transporters. The
methanol extract of Sideritis scardica inhibited the
uptake of [³H]-serotonin, [³H]-noradrenaline and
[³H]-dopamine into rat brain synaptosomes with
EC50 values of 31.0 µg/ml [16.4; 58.6] for serotonin
uptake, 42.3 µg/ml [31.8; 56.4] for noradrenaline
uptake and 37.0 µg/ml [27.5; 49.8] for dopamine
uptake (Figure 1). Maximum inhibition was 108%
± 6% for serotonin, 90% ± 6% for noradrenaline
and 89% ± 6% for dopamine uptake.
The water extract of Sideritis scardica also
inhibited the uptake of the monoamines with
similar EC50 values but mostly lower maximum
effects. EC50 values were 38.5 µg/ml [20.4; 72.8]
for serotonin uptake, 30.6 [25.1; 37.5] for
noradrenaline uptake and 45.5 [31.4; 66.0] for
dopamine uptake. Maximum inhibition was 70% ±
8% for serotonin, 122 % ± 13% for noradrenaline
and 57% ± 6% for dopamine uptake.
3.2 JAR cells (human serotonin transporter
hSERT)
3.2.1 Inhibition of hSERT by Sideritis scardica
extract
The concentration-response curve for the uptake of
serotonin by the human serotonin transporter
hSERT was recorded in this set of experiments.
Sideritis scardica methanol extract inhibited the
uptake of [³H]-serotonin into the human JAR cell
line with a EC50 of 1.4 µg/ml [0.6; 3.5] and a
maximum inhibition of 70% ± 9%. The 70%
ethanol extract showed in this system an EC50 value
of 55.9 µg/ml [31.6; 99.3] and a maximum
inhibition of 96% ± 12%.
3.2.2. Shift of the fluvoxamine dose-response
curve by Sideritis scardica 70% ethanol extract
We investigated the effect of various concentrations
of Sideritis on the inhibition of serotonin uptake by
fluvoxamine. The concentration-response curve of
fluvoxamine (EC50: 3.8 nM [2.2; 6.4]) was shifted
to the left by adding Sideritis ethanol extract.
Addition of 10 µg/ml Sideritis extract resulted in a
EC50 for the combination of Sideritis and
fluvoxamine of 1.5 nM [1.2; 1.8], addition of 50
3

µg/ml Sideritis extract yielded an EC50 of 0.5 nM
[0.3; 0.7] (Figure 2).
specific serotonin uptake
specific noradrenaline uptake
specific dopamine uptake
1,4
1,2
1,0
0,8
0,6
0,4
0,2
0,0
-0,2
-7 -6 -5 -4 -3
1,4
1,2
1,0
0,8
0,6
0,4
0,2
0,0
log [µg/ml]
-0,2
-7 -6 -5 -4 -3
1,4
1,2
1,0
0,8
0,6
0,4
0,2
0,0
log [µg/ml]
-0,2
-7 -6 -5 -4 -3
log [µg/ml]
Figure 1: Concentration-response curves of Sideritis scardica
methanol extract for the uptake of serotonin (A), noradrenaline
(B) and dopamine (C) into rat brain synaptosomes. Values are
expressed as mean ± S.E.M (n=8).
A
B
C
3.3. Effect of Sideritis scardica extracts on
cell viability
The LDH assay did not show differences between
controls and cells treated with methanolic Sideritis
scardica extract. Relative LDH activities in the
supernatant of the JAR cells were 107% ± 14%
specific serotonin uptake
with 50 µg/ml and 97% ± 16% with 500 µg/ml
Sideritis scardica extract.
1,6
1,4
1,2
1,0
0,8
0,6
0,4
0,2
0,0
-0,2
Shift of the fluvoxamine concentration-response curve
for the uptake of serotonin into human JAR cells
in presence of Sideritis scardica ethanol extract.
-0,4
-12 -10 -8 -6 -4
Figure 2: Shift of the fluvoxamine concentration-response curve
for the uptake of serotonin into human JAR cells in presence of
10 µg/ml and 50 µg/ml Sideritis scardica ethanol extract. Values
are expressed as mean ± S.E.M. (n=4).
4. Discussion
log [fluvoxamine]
Values are expressed as mean ± S.E.M. (n=4).
fluvoxamine
+10 µg/ml
+50 µg/ml
Previous pharmacological studies have
demonstrated that plants of the genus Sideritis have
anti-inflammatory (3,4), diuretic (7), antioxidant
(8), analgesic (9) and antibacterial and antifungal
(5,6) effects. The herbs are traditionally used
throughout the mediterranean regions for colds and
respiratory problems. They also are used as an antiinflammatory
remedy and to reduce fever. Tea from
Sideritis species has become very fashionable in
Germany recently, and is to be found in a wide
variety of shops. In this study, we have focussed on
the commercially available and farm-cultivated
species Sideritis scardica, one main constituent of
“Bergtee” in Germany and have determined its
pharmacological profile with drug-screening
models for the investigation of monoamine
transporter targeting established in our laboratory.
The results of the present study illustrate that
Sideritis scardica is a potent inhibitor of the
monoamine transporters. The water and alcoholic
extracts of Sideritis scardica inhibited the uptake of
serotonin, noradrenaline and dopamine by their
respective transporters in a concentration-dependent
manner. The inhibition of the human serotonin
transporter hSERT (expressed in human JAR cells)
by Sideritis scardica methanol extract was even
more pronounced than the inhibition of the rat brain
serotonin transporter.
Combining Sideritis scardica 70% ethanol extract
with fluvoxamine leads to a leftward shift of the
4

fluvoxamine concentration-response curve without
changing the maximum inhibition. Less
fluvoxamine is needed in the presence of Sideritis
scardica extract to elicit the same level of
biological response. This increase of drug
sensitivity is to be found even at concentrations of
Sideritis, which are per se not active at the
serotonin transporter. Sideritis extract increases the
apparent potency of fluvoxamine in a
concentration-dependent manner more than 8-fold,
which may be explained by a concerted interaction
of the two serotonin uptake blockers with the
serotonin transporter. Other effects than only
inhibiting serotonin transport like allosteric
modulation of the transporter or alteration of the
transporter activity by Sideritis scardica extracts
might also be considered.
The lactate dehydrogenase assay showed that
treatment of the JAR cells with Sideritis scardica
methanol extract at concentrations up to 500 µg/ml
did not affect cell viability. This demonstrates that
the inhibitory action of the extract on the
monoamine transporters does not appear to be due
to variation of cell viability.
In order to exert their mode of action in vivo, the
components of the Sideritis scardica extracts must
be able to cross the blood brain barrier to reach
their target site. Most drugs cross the blood brain
barrier by transmembrane diffusion. This is a nonsaturable
mechanism that depends on the melding
of the drug into the cell membrane. A high degree
of lipid solubility and low molecular weight favour
crossing by this mechanism. Reviews often quote a
cut-off of 400 to 600 g/mol. Other factors
influencing the ability of a drug to partition from
blood into the blood brain barrier include charge,
tertiary structure and degree of protein binding.
Mechanisms for the crossing of the blood brain
barrier also include saturable transporters,
adsorptive endocytosis and the extracellular
pathways (20). Substances which come into
consideration as active elements in the Sideritis
scardica extracts comprise, among others, terpenes,
flavonoids and phenols. These substances typically
show molecular weights in the range of 200 – 400
g/mol. They are soluble in alcohol or aqueous
alcohol and therefore are of a lipophilic character.
The Sideritis scardica extracts investigated in this
study are therefore likely to cross the blood brain
barrier by transmembrane diffusion.
Depressive disorders are characterised by an
imbalance in monoaminergic neurotransmission.
Based on findings from studies of antidepressants
treatment, it may be possible to assign specific
symptoms of depression to specific neurochemical
mechanisms. Serotonin may be related to anxiety,
obsessions and compulsions; noradrenaline to
alertness and energy as well as anxiety, attention
and interest in life; and dopamine to attention,
motivation, pleasure and reward as well as interest
in life (21). Increasing any of these three
neurotransmitters will elevate mood, but the other
elements of depression may be particularly
responsive to elevation of a certain
neurotransmitter. It is therefore desirable to have a
remedy which acts on as many monoaminergic
systems as possible.
Extracts of Hypericum perforatum have been used
since antiquity for the treatment of depressive
symptoms. The exact mechanisms of action are still
unclear, nevertheless randomised clinical trials have
shown that Hypericum extracts are more effective
than placebo and similarly effective as standard
antidepressants while having better tolerability in
the acute treatment of major depressive episodes. St
John's wort may rarely cause photosensitivity. This
can lead to visual sensitivity to light and to
sunburns in situations that would not normally
cause them. The most important risk associated
with Hypericum extracts are interactions with other
drugs. St John's wort has also been shown to cause
multiple drug interactions through induction of the
cytochrome P450 enzyme CYP3A4, but also
CYP2C9. This results in the increased metabolism
of those drugs, resulting in decreased concentration
and clinical effect. Examples of drugs causing
clinically-significant interactions with St John's
wort are antiretrovirals, hormonal contraceptives
and immunosuppressants (22).
A recent study on the Hypericum perforatum
extract Ze 117 showed that it interferes in three
ways with the individual uptakes of the monoamine
neurotransmitters. EC50 values for this extract were
54 µg/ml for noradrenaline uptake, 350 µg/ml for
dopamine uptake and 1600 µg/ml for serotonin
uptake (23). Therefore, the potency of the
noradrenaline uptake inhibition was around 30
times higher than that for serotonin, and seven
times higher than that of the dopamine uptake
inhibition. Combination of Hypericum perforatum
with other plant extracts like passion flower of
valerian improve the pharmacological profile of the
phytodrug by synergistic effects, the EC50 of an
ethanolic Hypericum extract for serotonin uptake
into rat brain slices was lowered from 177.5 µg/ml
for St. John’s wort extract alone to 37.2 µg/ml in
the presence of 200 µg/ml of Passiflora extract
(24).
In contrast to St. John’s wort, Sideritis scardica
extract has EC50 values for all three types of
monoamine transporters in the range of 30-40
µg/ml. With this background, the pharmacological
profile of Sideritis scardica extract might be
beneficial for the therapy of depressive disorders. It
elevates the extracellular concentration of all three
monoamine neurotransmitters by inhibiting their
transporters with similar potency and therefore
might ameliorate the symptoms of depression better
5

and more powerful than monospecific drugs. In
allopathic pharmacology the debate about the
advantage of dual action antidepressants like
venlafaxine and duloxetine is still going on (25,26).
Another possible application of Sideritis scardica
extracts as inhibitors of the monoamine transporters
consists in the therapy of attention-deficit
hyperactivity disorder (ADHD). This behavioural
disorder is characterised by inattention or lack of
focus, hyperactivity and impulsivity. These
symptoms have a childhood onset and often persist
into adolescence and adulthood. Estimates indicate
that 6- 9% of children and adolescents meet
diagnostic criteria for ADHD and that the
prevalence of ADHD in adults is around 3-5% (27).
Genetic data and collective evidence from
neurobiologic and neuropsychologic studies point
to a predominant involvement of the
catecholaminergic system in ADHD (17). Adequate
catecholaminergic modulation of the prefrontal
cortex, the brain region that plays an important role
in the physiology of cognition and emotion, is
essential for attention and vigilance. The
dysfunction of the prefrontal cortex in ADHD has
been attributed to a decreased catecholamine
function affecting cognition and motor inhibition.
Since monoamine transporters are (at least in part)
responsible for regulating extracellular
concentrations of the catecholamines noradrenaline
and dopamine, the common treatment of ADHD
includes stimulant medications with drugs like
methylphenidate. These stimulants block the
reuptake of noradrenaline and dopamine thus rising
their extracellular levels. Currently, the only
nonstimulant medication approved for the treatment
ADHD is atomoxetine, which selectively enhances
extracellular noradrenaline and dopamine levels
within the prefrontal cortex (28). Although
noradrenaline and dopamine are in the main focus
of pharmacological therapy of ADHD, an
additional contribution of the serotonergic system
can not be excluded. Recent genetic and
neuroimaging studies provide evidence for separate
contributions of altered dopamine and serotonin
function in this disorder (29). Most tricyclic
antidepressants acting on serotonin and
noradrenaline transporters are good remedies for
managing behavioural and, to some extent,
cognitive symptoms (30).
Some parents refuse a therapy of their children with
stimulants or chemical drugs due to the possible
side effects of these drugs. Therefore, a large
number of alternative medications of ADHD have
been praised. These remedies are often of a
questionable efficacy. Herbal medicines and natural
substances which are used for the treatment of
ADHD include Ginkgo biloba because of the
reputed beneficial effects of this plant upon the
brain (31,32). St. John's wort is also sometimes
used to try to help regulate mood and behaviour
problems associated with ADHD (33). But no one
of these herbal remedies has a proven mechanism
of action which would suggest the use of these
plant extracts for the treatment of ADHD or even a
proven efficacy for the treatment of ADHD until
today.
Sideritis scardica extracts inhibit all monoamine
transporters with approximately the same potency.
With this mode of action, they are the first
phytomedical entity with this proven mode of
action. All other remedies used in ADHD treatment
show selectivity towards only one of the three
transporters. Methylphenidate has higher affinity to
dopamine transporters than to noradrenaline
transporters and very low affinity for serotonin
transporters. Atomoxetine on the other hand
selectively inhibits noradrenaline transport, its
action at the serotonin transporter is weaker and it
shows a low affinity towards dopamine transporters
(28). Sideritis scardica extracts with their ability to
inhibit dopamine, noradrenaline and serotonin
uptake to the same extent may turn out to be
beneficial for a phytochemical therapy of ADHD.
5. Conclusions
Aqueous and alcoholic extracts of Sideritis scardica
are able to inhibit serotonin, noradrenaline and
dopamine transporters with similar EC50 values. By
inhibiting neurotransmitter reuptake the active
levels of the monoamines are elevated within the
synapse. This is a biochemical and pharmacological
mode of action which suggests to use Sideritis
scardica extracts for the treatment of disorders
associated with an altered or malfunctioning
monoaminergic neurotransmission. Sideritis
scardica extracts may be superior to other plant
extracts in the therapy of depressive disorders, since
the long-term traditional use in the mediterranean
area did not reveal side effects of the drug until
now. Sideritis scardica extracts also may have a
good potential to get a proof of action as the first
plant extract for the treatment of attention-deficit
hyperactivity disorder (ADHD).
Acknowledgements
This study was supported by a grant from the
Bundesministerium für Wirtschaft und Technologie
(ProInno II; KU 0004501 AJ4).
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Contact:
Dr. Rainer Knörle
IBAM GbR Dr. Rainer Knörle & Dr. Peter Schnierle, Ferdinand-Porsche-Strasse 5, D-79211 Denzlingen,
Germany, Tel +49 7666 884 5758; Fax +49 7666 884 5760 ; info@ibam.de
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